First Author | Arora PD | Year | 2004 |
Journal | Mol Biol Cell | Volume | 15 |
Issue | 2 | Pages | 588-99 |
PubMed ID | 14617805 | Mgi Jnum | J:90015 |
Mgi Id | MGI:3042311 | Doi | 10.1091/mbc.E03-07-0468 |
Citation | Arora PD, et al. (2004) Gelsolin mediates collagen phagocytosis through a rac-dependent step. Mol Biol Cell 15(2):588-99 |
abstractText | The role of gelsolin, a calcium-dependent actin-severing protein, in mediating collagen phagocytosis, is not defined. We examined alpha 2 beta 1 integrin-mediated phagocytosis in fibroblasts from wild-type (WT) and gelsolin knockout (Gsn(-)) mice. After initial contact with collagen beads, collagen binding and internalization were 60% lower in Gsn(-) than WT cells. This deficiency was restored by transfection with gelsolin or with beta1 integrin-activating antibodies. WT cells showed robust rac activation and increased [Ca(2+)](i) during early contact with collagen beads, but Gsn(-) cells showed very limited responses. Transfected gelsolin in Gsn(-) cells restored rac activation after collagen binding. Transfection of Gsn(-) cells with active rac increased collagen binding to WT levels. Chelation of intracellular calcium inhibited collagen binding and rac activation, whereas calcium ionophore induced rac activation in WT and Gsn(-) cells. We conclude that the ability of gelsolin to remodel actin filaments is important for collagen-induced calcium entry; calcium in turn is required for rac activation, which subsequently enhances collagen binding to unoccupied alpha 2 beta 1 integrins. |